Epigenetic and Neurological Impairments Associated with Early Life Exposure to Persistent Organic Pollutants

Figure 3

Three-hit hypothesis to explain the effect of an early exposure to pollutant on AD risk in late life. Exposure to pollutants in the neonatal period could impact epigenetic regulations. Late events could reactivate these regulations and affect Aβ accumulation or tau phosphorylation in the clinically silent phase which leads to MCI and clinically expressed AD. Mechanisms of Aβ accumulation in the brain: Aβ peptide could accumulate through 3 mechanisms: overproduction from APP, reduction of clearance through BBB, and inhibition of the various intracerebral degradation mechanisms. Increase of Aβo lead to synaptic dysfunctions, neuronal death, and memory alterations.